In the world of pharmaceuticals, companies are fighting for the rights to the process and the use of certain compounds and even certain combinations of compounds. This rush for use of ideas and need of profit has led to patent infringement. Intellectual property infringement is an excellent way to stunt the creative of our society. Without the rights to our inventions or our scientific finds what would be the motivation for most of today’s society? This is especially true in the pharmaceutical industry. Generic and brand name drugs are fighting for the rights to create and sell their drugs every day. The brand names are trying to keep their patents longer by slightly modifying the active ingredient or by going over the counter when their patent is ready to expire. Generic drugs are not innocent of the games either, they arebarging in to foreign countries to sell a generic version and not allow these inventors livelihood to what they created. One of the most recent battles was over the right to create a generic form of Allegra-D. This patent infringement case, settled on June 14, 2012, is a positive step in the right direction towards protecting the rights of invention.[1] This case is one of many that happen every day.
A patent applies to three main categories. These three main categories are a design patents, plant patents, and utility patents. The design patent would be for a decorative characteristic and a plant patent would be for an asexually produced plant. The most popul
Figure 1 is a diagram of the entire patent process [2]
ar and most encompassing would be a utility patent. This would include a process, machine, article of manufacture, composition of matter. Pharmaceuticals mostly fall under process, which protects the actual process of the compound. Once the type of patent is determined, the company or inventor determines how to file, either globally or nationally.[2] To file globally an invention needs to go through both the European Patent Office, also called the EPO, and Japanese Patent Office, also called the JPO. These are the recognized Patent Offices throughout the world.[3] If international rights are not needed, the United States provide either a provisional or nonprovisional patent. The main difference between a provisional and nonprovisional patent is who they are targeted to. A provisional patent is a way for an inventor to apply for a patent and allow them to have one year to apply for a nonprovisional patent.[4] The provisional application came into effect under the GATT Uruguay Round Agreements, which allowed an average joe to afford to protect their invention. This allows for the status of “Patent Pending” to be applied to their informal patent application.[5] This protects their rights to their inventions and gives them a chance to compete with big business. A nonprovisional patent tends to be more official and is examined by a patent examiner.[4] After choosing what type of patent and process the invention would need either the applicant or a patent attorney will go through filing, examinations by the United States Patent and Trade Office then will either receive a patent or will have to go through with appeals.[2] Below is a diagram of the patent process.
In the patent process, there are some ways to expedite the process. One of these special privileges is prioritized examination which is only granted to 10,000 applicants a year and tries to determine a final decision within a year.[6] There is also an accelerated examination option which will also give a verdict within a year, but this is more a restrictive process, which only applies to special types of patents such as health or age of the Patent Prosecution Highway (PPH), HIV/AIDS and cancer, environmental quality, manufacture, infringement, energy, recombinant DNA, superconductivity materials, biotechnology, and counter terrorism only filed by small entities.[7] This once again is another step into protecting the individual and small business from being crushed by the large corporations. The next expedited process is a pilot program called First Action Interview. This pilot program started October 20, 2009 and allows utility patents in the field of art to have an interview with the patent examiner. This helped resolve four main issues: the ability to go forward in the patent process, created more face to face time between examiner and inventor, allowed issues to be resolved early on in the process, and the ability to facilitate an early payment.[8] The last process is the Patent Prosecution Highway or PPH. This basically means if a patent is being approved in one country the patent can be expedited in another country. There are different request forms and policies between different nations.[9]
Allegra-D, which Albany Molecular Research Inc. holds the most recently disputed patent to, has gone through this process and is now looking to protect the rights to bar a generic version of Allegra-D from being put on the market. The United States Patent Number is 7,390,906 and is for the piperidine derivatives and process for their production.[1,10] Fexofenadine is a type of piperidine, and this patent protects the “substantially pure form” of all derivatives.[10] The patent for the piperidine derivatives allows Albany Molecular Research Inc. to be the sole distributor of this antihistamine until their patent expires. In the temporary restraining order against Dr. Reddy’s Laboratories Inc. and Dr. Reddy’s Laboratories LTD, the court issues a primary injunction and possible further relief, in fact agree with the fact that the Reddy company intrude on the ‘906 patent.[1] Looking at the case, it seems to be clear cut patent infringement, but Dr. Reddy’s Laboratories Inc. challenges a set of words used in the patent. They believed their product in generic form was substantially different from the patent because the process of patent ‘906 claimed to be a “substantially pure form”.[1] This did not prove to be substantial factor. The cyclopropyl ketone intermediate is the determining factor for this specific process and the fact that Dr. Reddy’s Laboratories also used such an intermediate to synthesis fexofenadine hydrochloride gave them no grounds to sell their generic product in the United States.[1]
The 7,390,906 Patent clearly walks through step by step procedure of every process they use to create piperdines. The overall process in the patent is taking the substantially pure regioisomers and converting them to a piperidine derivative with a keto group. This piperidine derivative compound is then reduced with a hydroxyl group. One way to create the initial substantially pure regioisomer is the actual matter of the patent and covers a Friedel-Crafts acylation of the initial compound. This compound is then hydrolyzed and then crystalized. Another way to create the substantially pure regioisomer is to start again with an acylation, which is in a hydrocarbon solvent and a catalyst. The last way to create the initial substantially pure regioisomer compound is by performing a Friedel-Crafts acylation then crystalizing and isolating the pure regioisomer. After this step there is two separate ways to convert this substantially pure regioisomer to the substantially pure piperidine derivative with a keto group. In the first way, the regioisomer is halogenated under specific conditions to become a first intermediate which will allow for the alkylation to become the piperidine derivative. The halogenation requires a suitable halogen nucleophile, Lewis Acid and solvent to open the ring. This intermediate is put through the appropriate alkylation and forms the piperidine derivative with keto group. The second way to obtain the piperidine derivative with keto group is to perform an alkylation with a Lewis Acid with a piperidine compound and the . Then a simple reduction of a keto group with the pure piperidine derivation would occur.[10]
Friedel-Crafts Acylation [11]
Friedel-Crafts Alkylation [12]
The ‘906 Patent covers all their bases and basically has rights to ever process of creating a piperidine derivative. Since they covered both acylation and alkylation in their patent, there is no room to tweak and create the same product without trampling over their rights. Whoever wrote this patent for Albany Molecular Research Inc. knew how to cover he basis and guaranteed the full span of their patent rights. Since an allergy medication relies on the antihistamine, Dr. Reddy’s Laboratories has to either synthesize fexofenadine hydrochloride by switching the actually reactions use or bypassing the intermediate step. To the best of my knowledge, that is impossible.
Albany Molecular Research Inc. also applied for global rights to their patent ‘906. They applied to the European Patent Office under the application number 94 920 762.5 or published as WO 95/00482. This patent was denied global recognition on January 28, 1997 due to the term substantially pure regioisomer.[13] This term gave advantage to Albany Molecular Research Inc. in the United States. This was because in the United States we focus on the protection of the creation while in the European Patent System is focusing on the technicality. This might be in part to how the European society is more creative and more willing to create then in the United States. Also the European Patent Office refuse the WO 95/00482 due to the multiple substitution spots of phenyl in regioisomers.[13]
Looking at different brand name pharmaceuticals, there tend to be similarities, but differences just to not tread on each other’s patents. There are three brand names over the counter allergy medicines in circulation today. Allegra-D is an allergy medicine that combines two active ingredients to act as an antihistamine and to reduce nasal decongestant. The antihistamine is 180 milligrams of fexofenadine hydrochloride and the nasal decongestant is 240 milligrams of pseudoephedrine hydrochloride for a twenty-four hour tablet.[14] The use of fexofenadine hydrochloride as an antihistamine is different in comparison to Allegra-D’s competitors. Claritin-D uses 10 milligrams of loratadine as the antihistamine and 240 milligrams of pseudoephedrine sulfate as the nasal decongestant for a twenty-four hour tablet.[15] Zyrtec-D uses 5 milligrams of cetirizine hydrochloride as the antihistamine and 120 milligrams of pseudoephedrine hydrochloride as the nasal decongestant for a twelve hour tablet.[16] These different combinations allow for each product to be effective in each person differently. All these allergy and nasal decongestants treat for the same symptoms: runny nose, sneezing, itchy and watery eyes, nose, and throat, and nasal congestion.[14-16] The only different use for Allegra-D is for sinus pressure.[14]
All the antihistamines belong to the piperdine family, but what separated them from being considered part of the ‘906 patent? For Zyrtec-D, their patent clearly covers their specific antihistamine, which is cetirizine. Their patent also speaks more to the effect of methods for treating this type of severe allergic reaction.[20] For Claritin-D, their patent protects the system of how their pill acts in relationship to their antihistamines and nasal decongestant. Their tablet has a three part system: the core, which is a concentrated section of decongestant, the coating, which is the delayed released that leads to the core, the immediate release of decongestant and antihistamine.[21] Also one thing that might be overlooked is that there are non-decongestant versions of all these medicines, which in return might also have their own patents. Each of these medicines once use to be a prescription filled medications, but now as over the counter they are susceptible to more and more obstacles with their patent rights.
Patents protect the creative rights of an individual and give hope to those who are in search for the next new discovery. These rights do come at a price for a small inventor, unknowledgeable employee, or a small company who unfortunately cannot afford or gain enough resources to complete a patent correctly. There are many loop holes that need to be covered when writing a patent, as was seen in the Allegra-D dispute. Money buys protection and unfortunately there has been a lack in creative in our society due to this injustice. Does the patent process protect the right people? Has the attempt to even the playing field been taken advantage of? What statistical proof is there to support the difference in creative between the United States Patent System and the European Patent System?
[10] "Patent US7390906 - Piperidine derivatives and process for their production - Google Patents." Google. N.p., n.d. Web. 8 Dec. 2012. <http://www.google.com/patents/US7390906>.
Allegra-D
In the world of pharmaceuticals, companies are fighting for the rights to the process and the use of certain compounds and even certain combinations of compounds. This rush for use of ideas and need of profit has led to patent infringement. Intellectual property infringement is an excellent way to stunt the creative of our society. Without the rights to our inventions or our scientific finds what would be the motivation for most of today’s society? This is especially true in the pharmaceutical industry. Generic and brand name drugs are fighting for the rights to create and sell their drugs every day. The brand names are trying to keep their patents longer by slightly modifying the active ingredient or by going over the counter when their patent is ready to expire. Generic drugs are not innocent of the games either, they arebarging in to foreign countries to sell a generic version and not allow these inventors livelihood to what they created. One of the most recent battles was over the right to create a generic form of Allegra-D. This patent infringement case, settled on June 14, 2012, is a positive step in the right direction towards protecting the rights of invention.[1] This case is one of many that happen every day.
A patent applies to three main categories. These three main categories are a design patents, plant patents, and utility patents. The design patent would be for a decorative characteristic and a plant patent would be for an asexually produced plant. The most popul
Figure 1 is a diagram of the entire patent process [2]
ar and most encompassing would be a utility patent. This would include a process, machine, article of manufacture, composition of matter. Pharmaceuticals mostly fall under process, which protects the actual process of the compound. Once the type of patent is determined, the company or inventor determines how to file, either globally or nationally.[2] To file globally an invention needs to go through both the European Patent Office, also called the EPO, and Japanese Patent Office, also called the JPO. These are the recognized Patent Offices throughout the world.[3] If international rights are not needed, the United States provide either a provisional or nonprovisional patent. The main difference between a provisional and nonprovisional patent is who they are targeted to. A provisional patent is a way for an inventor to apply for a patent and allow them to have one year to apply for a nonprovisional patent.[4] The provisional application came into effect under the GATT Uruguay Round Agreements, which allowed an average joe to afford to protect their invention. This allows for the status of “Patent Pending” to be applied to their informal patent application.[5] This protects their rights to their inventions and gives them a chance to compete with big business. A nonprovisional patent tends to be more official and is examined by a patent examiner.[4] After choosing what type of patent and process the invention would need either the applicant or a patent attorney will go through filing, examinations by the United States Patent and Trade Office then will either receive a patent or will have to go through with appeals.[2] Below is a diagram of the patent process.
In the patent process, there are some ways to expedite the process. One of these special privileges is prioritized examination which is only granted to 10,000 applicants a year and tries to determine a final decision within a year.[6] There is also an accelerated examination option which will also give a verdict within a year, but this is more a restrictive process, which only applies to special types of patents such as health or age of the Patent Prosecution Highway (PPH), HIV/AIDS and cancer, environmental quality, manufacture, infringement, energy, recombinant DNA, superconductivity materials, biotechnology, and counter terrorism only filed by small entities.[7] This once again is another step into protecting the individual and small business from being crushed by the large corporations. The next expedited process is a pilot program called First Action Interview. This pilot program started October 20, 2009 and allows utility patents in the field of art to have an interview with the patent examiner. This helped resolve four main issues: the ability to go forward in the patent process, created more face to face time between examiner and inventor, allowed issues to be resolved early on in the process, and the ability to facilitate an early payment.[8] The last process is the Patent Prosecution Highway or PPH. This basically means if a patent is being approved in one country the patent can be expedited in another country. There are different request forms and policies between different nations.[9]
Allegra-D, which Albany Molecular Research Inc. holds the most recently disputed patent to, has gone through this process and is now looking to protect the rights to bar a generic version of Allegra-D from being put on the market. The United States Patent Number is 7,390,906 and is for the piperidine derivatives and process for their production.[1,10] Fexofenadine is a type of piperidine, and this patent protects the “substantially pure form” of all derivatives.[10] The patent for the piperidine derivatives allows Albany Molecular Research Inc. to be the sole distributor of this antihistamine until their patent expires. In the temporary restraining order against Dr. Reddy’s Laboratories Inc. and Dr. Reddy’s Laboratories LTD, the court issues a primary injunction and possible further relief, in fact agree with the fact that the Reddy company intrude on the ‘906 patent.[1] Looking at the case, it seems to be clear cut patent infringement, but Dr. Reddy’s Laboratories Inc. challenges a set of words used in the patent. They believed their product in generic form was substantially different from the patent because the process of patent ‘906 claimed to be a “substantially pure form”.[1] This did not prove to be substantial factor. The cyclopropyl ketone intermediate is the determining factor for this specific process and the fact that Dr. Reddy’s Laboratories also used such an intermediate to synthesis fexofenadine hydrochloride gave them no grounds to sell their generic product in the United States.[1]
The 7,390,906 Patent clearly walks through step by step procedure of every process they use to create piperdines. The overall process in the patent is taking the substantially pure regioisomers and converting them to a piperidine derivative with a keto group. This piperidine derivative compound is then reduced with a hydroxyl group. One way to create the initial substantially pure regioisomer is the actual matter of the patent and covers a Friedel-Crafts acylation of the initial compound. This compound is then hydrolyzed and then crystalized. Another way to create the substantially pure regioisomer is to start again with an acylation, which is in a hydrocarbon solvent and a catalyst. The last way to create the initial substantially pure regioisomer compound is by performing a Friedel-Crafts acylation then crystalizing and isolating the pure regioisomer. After this step there is two separate ways to convert this substantially pure regioisomer to the substantially pure piperidine derivative with a keto group. In the first way, the regioisomer is halogenated under specific conditions to become a first intermediate which will allow for the alkylation to become the piperidine derivative. The halogenation requires a suitable halogen nucleophile, Lewis Acid and solvent to open the ring. This intermediate is put through the appropriate alkylation and forms the piperidine derivative with keto group. The second way to obtain the piperidine derivative with keto group is to perform an alkylation with a Lewis Acid with a piperidine compound and the . Then a simple reduction of a keto group with the pure piperidine derivation would occur.[10]
Friedel-Crafts Acylation [11]
Friedel-Crafts Alkylation [12]
The ‘906 Patent covers all their bases and basically has rights to ever process of creating a piperidine derivative. Since they covered both acylation and alkylation in their patent, there is no room to tweak and create the same product without trampling over their rights. Whoever wrote this patent for Albany Molecular Research Inc. knew how to cover he basis and guaranteed the full span of their patent rights. Since an allergy medication relies on the antihistamine, Dr. Reddy’s Laboratories has to either synthesize fexofenadine hydrochloride by switching the actually reactions use or bypassing the intermediate step. To the best of my knowledge, that is impossible.
Albany Molecular Research Inc. also applied for global rights to their patent ‘906. They applied to the European Patent Office under the application number 94 920 762.5 or published as WO 95/00482. This patent was denied global recognition on January 28, 1997 due to the term substantially pure regioisomer.[13] This term gave advantage to Albany Molecular Research Inc. in the United States. This was because in the United States we focus on the protection of the creation while in the European Patent System is focusing on the technicality. This might be in part to how the European society is more creative and more willing to create then in the United States. Also the European Patent Office refuse the WO 95/00482 due to the multiple substitution spots of phenyl in regioisomers.[13]
Looking at different brand name pharmaceuticals, there tend to be similarities, but differences just to not tread on each other’s patents. There are three brand names over the counter allergy medicines in circulation today. Allegra-D is an allergy medicine that combines two active ingredients to act as an antihistamine and to reduce nasal decongestant. The antihistamine is 180 milligrams of fexofenadine hydrochloride and the nasal decongestant is 240 milligrams of pseudoephedrine hydrochloride for a twenty-four hour tablet.[14] The use of fexofenadine hydrochloride as an antihistamine is different in comparison to Allegra-D’s competitors. Claritin-D uses 10 milligrams of loratadine as the antihistamine and 240 milligrams of pseudoephedrine sulfate as the nasal decongestant for a twenty-four hour tablet.[15] Zyrtec-D uses 5 milligrams of cetirizine hydrochloride as the antihistamine and 120 milligrams of pseudoephedrine hydrochloride as the nasal decongestant for a twelve hour tablet.[16] These different combinations allow for each product to be effective in each person differently. All these allergy and nasal decongestants treat for the same symptoms: runny nose, sneezing, itchy and watery eyes, nose, and throat, and nasal congestion.[14-16] The only different use for Allegra-D is for sinus pressure.[14]
Allegra-D antihistamine (Fexofenadine hydrochloride) [17]
Claritin-D antihistamine (Loratadine) [18]
Zyrtec-D antihistamine (Cetirizine) [19]
All the antihistamines belong to the piperdine family, but what separated them from being considered part of the ‘906 patent? For Zyrtec-D, their patent clearly covers their specific antihistamine, which is cetirizine. Their patent also speaks more to the effect of methods for treating this type of severe allergic reaction.[20] For Claritin-D, their patent protects the system of how their pill acts in relationship to their antihistamines and nasal decongestant. Their tablet has a three part system: the core, which is a concentrated section of decongestant, the coating, which is the delayed released that leads to the core, the immediate release of decongestant and antihistamine.[21] Also one thing that might be overlooked is that there are non-decongestant versions of all these medicines, which in return might also have their own patents. Each of these medicines once use to be a prescription filled medications, but now as over the counter they are susceptible to more and more obstacles with their patent rights.
Patents protect the creative rights of an individual and give hope to those who are in search for the next new discovery. These rights do come at a price for a small inventor, unknowledgeable employee, or a small company who unfortunately cannot afford or gain enough resources to complete a patent correctly. There are many loop holes that need to be covered when writing a patent, as was seen in the Allegra-D dispute. Money buys protection and unfortunately there has been a lack in creative in our society due to this injustice. Does the patent process protect the right people? Has the attempt to even the playing field been taken advantage of? What statistical proof is there to support the difference in creative between the United States Patent System and the European Patent System?
Media Option
http://www.youtube.com/watch?v=N2OAXfTm1tA&feature=youtu.be
Works Cited
[1] Elfin, Dana A. . "In Win for Sanofi, District Court Blocks Dr. Reddy's Introduction of Generic Allegra-D." Pharmaceutical Law & Industry Report 2012 (2012): n. pag. Bloomberg BNA. Web. 16 Nov. 2012. http://op.bna.com.ezproxy2.library.drexel.edu/hl.nsf/r?Open=deln-86fl4e.
[2]"Process for Obtaining a Utility Patent." United States Patent and Trademark Office. N.p., n.d. Web. 29 Nov. 2012. <http://www.uspto.gov/patents/process/index.jsp>.
[3] "International Protection." United States Patent and Trademark Office. N.p., n.d. Web. 20 Nov. 2012. <http://www.uspto.gov/patents/int_protect/index.jsp>.
[4] "Nonprovisional (Utility) Patent Application Filing Guide." United States Patent and Trademark Office. N.p., n.d. Web. 23 Nov. 2012. <http://www.uspto.gov/patents/resources/types/utility.jsp>.
[5] "Provisional Application for Patent." United States Patent and Trademark Office. N.p., n.d. Web. 23 Nov. 2012. <http://www.uspto.gov/patents/resources/types/provapp.jsp>.
[6] "Patents Examination." United States Patent and Trademark Office. N.p., n.d. Web. 24 Nov. 2012. <http://www.uspto.gov/aia_implementation/patents.jsp#heading-5>.
[7] "Accelerated Examination." United States Patent and Trademark Office. N.p., n.d. Web. 23 Nov. 2012. <http://www.uspto.gov/patents/process/file/accelerated/index.jsp>.
[8] "First Action Interview Pilot Program." United States Patent and Trademark Office. N.p., n.d. Web. 24 Nov. 2012. <http://www.uspto.gov/patents/init_events/faipp_landing.jsp>.
[9] "Patent Prosecution Highway (PPH) - Fast Track Examination of Applications." United States Patent and Trademark Office. N.p., n.d. Web. 25 Nov. 2012. <http://www.uspto.gov/patents/init_events/pph/index.jsp>.
[10] "Patent US7390906 - Piperidine derivatives and process for their production - Google Patents." Google. N.p., n.d. Web. 8 Dec. 2012. <http://www.google.com/patents/US7390906>.
[11] "Friedel-Crafts Acylation." Organic Chemistry Portal. N.p., n.d. Web. 27 Nov. 2012. <http://www.organic-chemistry.org/namedreactions/friedel-crafts-acylation.shtm>.
[12] "Friedel-Crafts Alkylation." Organic Chemistry Portal. N.p., n.d. Web. 27 Nov. 2012. <http://www.organic-chemistry.org/namedreactions/friedel-crafts-alkylation.shtm>.
[13] "EPO - T 0957/96 (Unity of Invention/ALBANY) of 28.1.1997." EPO - Home. N.p., n.d. Web. 28 Nov. 2012. <http://www.epo.org/law-practice/case-law-appeals/recent/t960957eu1.html>.
[14] "Allegra Products | Allergy Relief From Indoor and Outdoor Allergies | Allegra." 24-Hour Relief From Indoor and Outdoor Allergies | Allegra. N.p., n.d. Web. 3 Dec. 2012. <http://www.allegra.com/products.aspx#>.
[15] "Claritin D 24 Hour - Sinus and Allergy Relief | Claritin®." Claritin. N.p., n.d. Web. 3 Dec. 2012. <http://www.claritin.com/claritin/en/products/ClaritinD24Hour.jspa>.
[16] "ZYRTEC®-D Allergy Treatment & Decongestant - ZYRTEC®." ZYRTEC® Allergy Medication for Adults & Children - ZYRTEC®. N.p., n.d. Web. 3 Dec. 2012. <http://www.zyrtec.com/products/adults/zyrtec-d>.
[17] “2-[4-(1-Hydroxy-4-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}butyl)phenyl]-2-methylpropansa¤urehydrochlorid | C32H40ClNO4 | ChemSpider." ChemSpider | The free chemical database. N.p., n.d. Web. 5 Dec. 2012. <http://www.chemspider.com/Chemical-Structure.56703.html?rid=fd8be920-6fee-4d9e-9277-3e002b02f8db>.
[18] “Loratadine | C22H23ClN2O2 | ChemSpider." ChemSpider | The free chemical database. N.p., n.d. Web. 5 Dec. 2012. <http://www.chemspider.com/Chemical-Structure.3820.html?rid=ef2feb55-6baf-4936-8cfc-f1077c86206e>.
[19] “Cetirizine | C21H25ClN2O3 | ChemSpider." ChemSpider | The free chemical database. N.p., n.d. Web. 5 Dec. 2012. <http://www.chemspider.com/Chemical-Structure.2577.html?rid=871dc116-199a-4908-acdd-8c19dd104c32>.
[20] "United States Patent: 8314083." Page 1 of 1 . N.p., n.d. Web. 4 Dec. 2012. <http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=Zyrtec-D&OS=Zyrtec-D&RS=Zyrtec-D>.
[21] "Patent US8092831 - Antihistamine and decongestant system - Google Patents." Google. N.p., n.d. Web. 4 Dec. 2012. <http://www.google.com/patents/US8092831>.